phaidra.vetmeduni.ac.at o:5116 DOI 10.1186/s40635-025-00815-y Hypothermia after Cardiac Arrest in Large Animals (HACA-LA): a randomized controlled experimental study Background Induced hypothermia after cardiac arrest is neuroprotective in several animal models of cardiac arrest, but few high-quality studies have been conducted in larger animals. Recent clinical trials have questioned the beneficial effects of post-ischemic hypothermia. This study investigated whether immediate cooling or a 2-h delay in cooling to 33 °C after cardiac arrest was neuroprotective compared to controlled normothermia in large animals. Methods Young adult female swine were anesthetized and kept at normothermia (38 °C). All animals were subject to 10 min of cardiac arrest by ventricular fibrillation, followed by 4 min of cardiopulmonary resuscitation, before the first countershock. At 10 min of return of spontaneous circulation (ROSC), animals were included and randomized to receive immediate hypothermia (33 °C), 2-h delayed hypothermia (33 °C), or normothermia for 30 h, including both cooling and rewarming time. Animals were extubated and assessed for 7 days. The primary outcome was brain histopathology using a modified Histology Damage Score. Secondary outcomes were neurocognitive testing, neurologic deficit score, and biomarkers of brain injury. Results Among 42 animals, 33 were included; 11 in each arm, 23 survived until day 7. The modified Histology Damage Score was not significantly different between groups (p = 0.29). Neither neurocognitive testing nor neurologic deficit scores showed significant differences between the groups (p = 0.11 and p = 0.67, respectively). Neurofilament light chain (NfL) levels were significantly lower in the immediate hypothermia group at 48 h and on day 7 compared to the normothermia group (p = 0.0087, p = 0.012), but not in the delayed hypothermia group (p = 0.075, p = 0.33). Conclusion Our experimental model in large swine showed no neuropathological or functional protective effect of induced hypothermia after cardiac arrest, but NfL levels were lower in animals receiving immediately induced hypothermia, suggesting mitigation of neuronal injury. eng Cardiac Arrest Hypothermia Temperature Control Neuronal Damage Functional Outcome Neurofilament Light Chain (NfL) Swine 2026-05-08T08:32:01.450Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Persson;Olof; FN:Olof Persson X-ORCID:https://orcid.org/0009-0007-1102-1156 END:VCARD BEGIN:VCARD VERSION:3.0 N:Valerianova;Anna; FN:Anna Valerianova END:VCARD BEGIN:VCARD VERSION:3.0 N:Tejkl;Leos; FN:Leos Tejkl END:VCARD BEGIN:VCARD VERSION:3.0 N:Bělohlávek;Jan; FN:Jan Bělohlávek END:VCARD BEGIN:VCARD VERSION:3.0 N:Cronberg;Tobias; FN:Tobias Cronberg END:VCARD BEGIN:VCARD VERSION:3.0 N:Nielsen;Niklas; FN:Niklas Nielsen END:VCARD BEGIN:VCARD VERSION:3.0 N:Frigyesi;Attila; FN:Attila Frigyesi END:VCARD BEGIN:VCARD VERSION:3.0 N:Ullén;Susann; FN:Susann Ullén END:VCARD BEGIN:VCARD VERSION:3.0 N:Weihs;Wolfgang; FN:Wolfgang Weihs END:VCARD BEGIN:VCARD VERSION:3.0 N:Stommel;Alexandra-Maria; FN:Alexandra-Maria Stommel END:VCARD BEGIN:VCARD VERSION:3.0 N:Blennow;Kaj; FN:Kaj Blennow END:VCARD BEGIN:VCARD VERSION:3.0 N:Zetterberg;Henrik; FN:Henrik Zetterberg END:VCARD BEGIN:VCARD VERSION:3.0 N:Högler;Sandra; FN:Sandra Högler X-ORCID:https://orcid.org/0000-0002-6899-5273 END:VCARD BEGIN:VCARD VERSION:3.0 N:Englund;Elisabet; FN:Elisabet Englund END:VCARD BEGIN:VCARD VERSION:3.0 N:Mlček;Mikuláš; FN:Mikuláš Mlček END:VCARD BEGIN:VCARD VERSION:3.0 N:Friberg;Hans; FN:Hans Friberg END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 2649817 https://phaidra.vetmeduni.ac.at/o:5116 https://phaidra.vetmeduni.ac.at/api/object/o:5116/thumbnail LOMv1.0 discipline